LYN

Last updated
LYN
PDB 1wa7 EBI.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases LYN , LYN proto-oncogene, Src family tyrosine kinase, JTK8, p53Lyn, p56Lyn
External IDs OMIM: 165120 MGI: 96892 HomoloGene: 55649 GeneCards: LYN
Orthologs
SpeciesHumanMouse
Entrez

4067

17096

Ensembl

ENSG00000254087

ENSMUSG00000042228

UniProt

P07948

P25911

RefSeq (mRNA)

NM_001111097
NM_002350

NM_001111096
NM_010747

RefSeq (protein)

NP_001104567
NP_002341

NP_001104566
NP_034877

Location (UCSC) Chr 8: 55.88 – 56.01 Mb Chr 4: 3.68 – 3.81 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tyrosine-protein kinase Lyn is a protein that in humans is encoded by the LYN gene. [5]

Contents

Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, [6] in neural tissues [7] liver, and adipose tissue. [8] In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. In these cells, a small amount of LYN is associated with cell surface receptor proteins, including the B cell antigen receptor (BCR), [9] [10] CD40, [11] or CD19. [12] The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the Src kinase family.

Function

Lyn has been described to have an inhibitory role in myeloid lineage proliferation. [13] Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation. LYN activation triggers a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phosholipase Cγ2 (PLCγ2) and phosphatidyl inositol-3 kinase. [12] [14] These kinases provide activation signals, which play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FCγRIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1, [15] [16] [17] [18] [19] which further downmodulate signaling pathways, attenuate cell activation and can mediate tolerance. In B cells, Lyn sets the threshold of cell signaling and maintains the balance between activation and inhibition. Lyn thus functions as a rheostat that modulates signaling rather than as a binary on-off switch. [20] [21] [22] HSP90 inhibitor NVP-BEP800 has been described to affect stability of LYN kinase and growth of B-cell acute lymphoblastic leukemias through inhibition of the NF-kappaB signaling. [23]

LYN is reported to be a key signal mediator for estrogen-dependent suppression of human osteoclast differentiation, survival, and function. [24] Lyn has also been implicated to have a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1). This phosphorylation of IRS1 leads to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. [25] In turn, activation of the insulin receptor has been shown to increase autophosphorylation of Lyn suggesting a possible feedback loop. [26] The insulin secretagogue, glimepiride (Amaryl®) activates Lyn in adipocytes via the disruption of lipid rafts. [27] This indirect Lyn activation may modulate the extrapancreatic glycemic control activity of glimepiride. [27] [28] Tolimidone (MLR-1023) is a small molecule allosteric activator of lyn kinase with an EC50 of 63 nM [29] [30] that is currently under Phase 2a investigation for Type II diabetes. [31] In June, 2016, the sponsor of these studies, Melior Discovery, announced positive results from their Phase 2a study with tolimidone in diabetic patients, [32] [33] and the continuation of additional clinical studies. [34]

Lyn has been shown to protect against hepatocellular apoptosis and promote liver regeneration through the preservation of hepatocellular mitochondrial integrity. [35]

Several investigators have shown the role of lyn kinase in different aspects of pulmonary function. Lyn activation in pulmonary epithelium has been shown to be important in improving pulmonary barrier integrity and to reduce edema. [36] [37] Additional evidence suggest that lyn activation in alveolar phagocytes improves phagocytosis of bacteria and reduces pulmonary infection. [38] [39] Finally, other research has found that lyn activation reduces pulmonary hypersecretion of mucus. [40]


Pathology

Much of the current knowledge about Lyn has emerged from studies of genetically manipulated mice. Lyn deficient mice display a phenotype that includes splenomegaly, a dramatic increase in numbers of myeloid progenitors and monocyte/macrophage tumors. Biochemical analysis of cells from these mutants revealed that Lyn is essential in establishing ITIM-dependent inhibitory signaling and for activation of specific protein tyrosine phosphatases within myeloid cells. [13]

Mice that expressed a hyperactive Lyn allele were tumor free and displayed no propensity toward hematological malignancy. These mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. With age these animals developed a glomerulonephritis phenotype associated with a 30% reduction in life expectancy. [41]

Interactions

LYN has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Lck</span> Lymphocyte protein

Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">Receptor tyrosine kinase</span> Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

<span class="mw-page-title-main">GRB2</span> Protein-coding gene in the species Homo sapiens

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">Tyrosine-protein kinase SYK</span>

Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene.

<span class="mw-page-title-main">CD22</span> Lectin molecule

CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.

<span class="mw-page-title-main">Lymphocyte cytosolic protein 2</span> Protein-coding gene in the species Homo sapiens

Lymphocyte cytosolic protein 2, also known as LCP2 or SLP-76, is a signal-transducing adaptor protein expressed in T cells and myeloid cells and is important in the signaling of T-cell receptors (TCRs). As an adaptor protein, SLP-76 does not have catalytic functions, primarily binding other signaling proteins to form larger signaling complexes. It is a key component of the signaling pathways of receptors with immunoreceptor tyrosine-based activation motifs (ITAMs) such as T-cell receptors, its precursors, and receptors for the Fc regions of certain antibodies. SLP-76 is expressed in T-cells and related lymphocytes like natural killer cells.

<span class="mw-page-title-main">Linker for activation of T cells</span> Protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

<span class="mw-page-title-main">Janus kinase 2</span> Non-receptor tyrosine kinase and coding gene in humans

Janus kinase 2 is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors.

<span class="mw-page-title-main">FYN</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

<span class="mw-page-title-main">PRKCD</span> Protein-coding gene in the species Homo sapiens

Protein kinase C delta type is an enzyme that in humans is encoded by the PRKCD gene.

<span class="mw-page-title-main">PIK3R1</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.

<span class="mw-page-title-main">PTPN6</span> Protein-coding gene in humans

Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.

<span class="mw-page-title-main">PLCG1</span> Protein-coding gene in the species Homo sapiens

Phospholipase C, gamma 1, also known as PLCG1 and PLCgamma1, is a protein that in humans involved in cell growth, migration, apoptosis, and proliferation. It is encoded by the PLCG1 gene and is part of the PLC superfamily.

<span class="mw-page-title-main">CRKL</span> Protein-coding gene in the species Homo sapiens

Crk-like protein is a protein that in humans is encoded by the CRKL gene.

<span class="mw-page-title-main">DOK1</span> Protein-coding gene in the species Homo sapiens

Docking protein 1 is a protein that in humans is encoded by the DOK1 gene.

<span class="mw-page-title-main">PTK2B</span> Protein-coding gene in the species Homo sapiens

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.

<span class="mw-page-title-main">INPP5D</span> Protein-coding gene in the species Homo sapiens

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.

<span class="mw-page-title-main">B-cell linker</span> Mammalian protein found in Homo sapiens

B-cell linker (BLNK) protein is expressed in B cells and macrophages and plays a large role in B cell receptor signaling. Like all adaptor proteins, BLNK has no known intrinsic enzymatic activity. Its function is to temporally and spatially coordinate and regulate downstream signaling effectors in B cell receptor (BCR) signaling, which is important in B cell development. Binding of these downstream effectors is dependent on BLNK phosphorylation. BLNK is encoded by the BLNK gene and is also known as SLP-65, BASH, and BCA.

<span class="mw-page-title-main">Tyrosine-protein kinase CSK</span> Kinase enzyme that phosphorylates Src-family kinases

Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, FYN, LCK, LYN and YES1.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000254087 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042228 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Yamanashi Y, Fukushige S, Semba K, Sukegawa J, Miyajima N, Matsubara K, Yamamoto T, Toyoshima K (Jan 1987). "The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck". Molecular and Cellular Biology. 7 (1): 237–43. doi:10.1128/MCB.7.1.237. PMC   365062 . PMID   3561390.
  6. ↑ Yamanashi Y, Mori S, Yoshida M, Kishimoto T, Inoue K, Yamamoto T, Toyoshima K (Sep 1989). "Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I". Proceedings of the National Academy of Sciences of the United States of America. 86 (17): 6538–42. Bibcode:1989PNAS...86.6538Y. doi: 10.1073/pnas.86.17.6538 . PMC   297879 . PMID   2505253.
  7. ↑ Umemori H, Wanaka A, Kato H, Takeuchi M, Tohyama M, Yamamoto T (Dec 1992). "Specific expressions of Fyn and Lyn, lymphocyte antigen receptor-associated tyrosine kinases, in the central nervous system". Brain Research. Molecular Brain Research. 16 (3–4): 303–10. doi:10.1016/0169-328X(92)90239-8. PMID   1337939.
  8. ↑ Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC (Feb 2010). "Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1". Cell Metabolism. 11 (2): 113–124. doi:10.1016/j.cmet.2009.12.010. PMC   2830006 . PMID   20142099.
  9. ↑ Yamamoto T, Yamanashi Y, Toyoshima K (Apr 1993). "Association of Src-family kinase Lyn with B-cell antigen receptor". Immunological Reviews. 132: 187–206. doi:10.1111/j.1600-065X.1993.tb00843.x. PMID   8349296. S2CID   10782326.
  10. ↑ Campbell MA, Sefton BM (May 1992). "Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases". Molecular and Cellular Biology. 12 (5): 2315–21. doi:10.1128/MCB.12.5.2315. PMC   364403 . PMID   1569953.
  11. ↑ Ren CL, Morio T, Fu SM, Geha RS (Feb 1994). "Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamma 2". The Journal of Experimental Medicine. 179 (2): 673–80. doi:10.1084/jem.179.2.673. PMC   2191357 . PMID   7507510.
  12. 1 2 Campbell 1999
  13. 1 2 Harder KW, Parsons LM, Armes J, Evans N, Kountouri N, Clark R, Quilici C, Grail D, Hodgson GS, Dunn AR, Hibbs ML (Oct 2001). "Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage". Immunity. 15 (4): 603–615. doi: 10.1016/S1074-7613(01)00208-4 . PMID   11672542.
  14. ↑ Yamanashi Y, Fukui Y, Wongsasant B, Kinoshita Y, Ichimori Y, Toyoshima K, Yamamoto T (Feb 1992). "Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling". Proceedings of the National Academy of Sciences of the United States of America. 89 (3): 1118–22. Bibcode:1992PNAS...89.1118Y. doi: 10.1073/pnas.89.3.1118 . PMC   48397 . PMID   1371009.
  15. ↑ Cornall RJ, Cyster JG, Hibbs ML, Dunn AR, Otipoby KL, Clark EA, Goodnow CC (Apr 1998). "Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection". Immunity. 8 (4): 497–508. doi: 10.1016/S1074-7613(00)80554-3 . PMID   9586639.
  16. ↑ Smith KG, Tarlinton DM, Doody GM, Hibbs ML, Fearon DT (Mar 1998). "Inhibition of the B cell by CD22: a requirement for Lyn". The Journal of Experimental Medicine. 187 (5): 807–11. doi:10.1084/jem.187.5.807. PMC   2212179 . PMID   9480991.
  17. ↑ Chan VW, Lowell CA, DeFranco AL (May 1998). "Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes". Current Biology. 8 (10): 545–53. Bibcode:1998CBio....8..545C. doi: 10.1016/S0960-9822(98)70223-4 . PMID   9601638. S2CID   12195731.
  18. ↑ Nishizumi H, Horikawa K, Mlinaric-Rascan I, Yamamoto T (Apr 1998). "A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals". The Journal of Experimental Medicine. 187 (8): 1343–8. doi:10.1084/jem.187.8.1343. PMC   2212230 . PMID   9547345.
  19. ↑ Maeda A, Scharenberg AM, Tsukada S, Bolen JB, Kinet JP, Kurosaki T (Apr 1999). "Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1". Oncogene. 18 (14): 2291–7. doi: 10.1038/sj.onc.1202552 . PMID   10327049.
  20. ↑ Lowell CA (Jul 2004). "Src-family kinases: rheostats of immune cell signaling". Molecular Immunology. 41 (6–7): 631–43. doi:10.1016/j.molimm.2004.04.010. PMID   15220000.
  21. ↑ Saijo K, Schmedt C, Su IH, Karasuyama H, Lowell CA, Reth M, Adachi T, Patke A, Santana A, Tarakhovsky A (Mar 2003). "Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development". Nature Immunology. 4 (3): 274–9. doi:10.1038/ni893. PMID   12563261. S2CID   32559368.
  22. ↑ Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM (Jan 2005). "Lyn tyrosine kinase: accentuating the positive and the negative". Immunity. 22 (1): 9–18. doi: 10.1016/j.immuni.2004.12.004 . PMID   15664155.
  23. ↑ Mshaik R, Simonet J, Georgievski A, Jamal L, Bechoua S, Ballerini P, Bellaye PS, Mlamla Z, Pais de Barros JP, Geissler A, Francin PJ, Girodon F, Garrido C, Quéré R (March 2021). "HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemia". Blood Cancer J. 3 (11): 61. doi: 10.1038/s41408-021-00450-2 . PMC   7973815 . PMID   33737511.
  24. ↑ Gavali S, Gupta MK, Daswani B, Wani MR, Sirdeshmukh R, Khatkhatay MI (March 2019). "LYN, a key mediator in estrogen-dependent suppression of osteoclast differentiation, survival, and function". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1865 (3): 547–557. doi: 10.1016/j.bbadis.2018.12.016 . PMID   30579930.
  25. ↑ Müller G, Wied S, Frick W (Jul 2000). "Cross talk of pp125(FAK) and pp59(Lyn) non-receptor tyrosine kinases to insulin-mimetic signaling in adipocytes". Molecular and Cellular Biology. 20 (13): 4708–4723. doi:10.1128/mcb.20.13.4708-4723.2000. PMC   85892 . PMID   10848597.
  26. ↑ Anderwald C, Müller G, Koca G, Fürnsinn C, Waldhäusl W, Roden M (Jul 2002). "Short-term leptin-dependent inhibition of hepatic gluconeogenesis is mediated by insulin receptor substrate-2". Molecular Endocrinology. 16 (7): 1612–1628. doi: 10.1210/mend.16.7.0867 . PMID   12089355.
  27. 1 2 Müller G (Nov 2000). "The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug Amaryl". Molecular Medicine. 6 (11): 907–933. doi:10.1007/BF03401827. PMC   1949923 . PMID   11147570.
  28. ↑ Müller G, Schulz A, Wied S, Frick W (Mar 2005). "Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes". Biochemical Pharmacology. 69 (5): 761–780. doi:10.1016/j.bcp.2004.11.014. PMID   15710354.
  29. ↑ Ochman AR, Lipinski CA, Handler JA, Reaume AG, Saporito MS (2012). "The Lyn kinase activator MLR-123 is a novel insulin receptor potentiator that elicits a rapid-onset and durable improvement in glucose homeostasis in animal models of type 2 diabetes". J Pharmacol Exp Ther. 342 (1): 23–32. doi:10.1124/jpet.112.192187. PMID   22431203. S2CID   7288053.[ permanent dead link ]
  30. ↑ Saporito MS, Ochman AR, Lipinski CA, Handler JA, Reaume AG (2011). "MLR-1023 is potent and selective allosteric activator of Lyn kinase in vitro that improves glucose tolerance in vivo". Journal of Pharmacology and Experimental Therapeutics. 342 (1): 15–22. doi:10.1124/jpet.112.192096. PMID   22473614. S2CID   26419896.
  31. ↑ "Melior Pharmaceuticals Initiates Phase 2 Study with MLR-1023 for Type 2 Diabetes". Business Wire. 3 March 2015. Retrieved March 3, 2015.
  32. ↑ "Melior Pharmaceuticals Announces Positive Phase 2A Results in Type 2 Diabetes Study". www.businesswire.com. 13 June 2016. Retrieved 2017-08-04.
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  34. ↑ "Melior Discovery website press releases". Archived from the original on 2018-05-17. Retrieved 2018-06-11.
  35. ↑ Gringeri E, Carraro A, Tibaldi E, D'Amico FE, Mancon M, Toninello A, Pagano MA, Vio C, Cillo U, Brunati AM (December 2009). "Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration" (PDF). The Biochemical Journal. 425 (2): 401–12. doi:10.1042/BJ20090902. PMID   19832701.
  36. ↑ Jan J, Zhang G, Welch EJ, Liang Y, Fu J, Vogel SM, Lowell CA, Du X, Cheresh DA, Malik AB, Li Z (Dec 2013). "A critical role for Lyn kinase in strengthening endothelial integrity and barrier function". Blood. 122 (25): 4140–4149. doi: 10.1182/blood-2013-03-491423 . PMC   3862279 . PMID   24108461.
  37. ↑ Corey SJ, Day RM (Dec 2013). "Shockingly: the loss of Lyn leads to leakiness". Blood. 122 (25): 4009–4010. doi:10.1182/blood-2013-10-533158. PMC   3862277 . PMID   24335031.
  38. ↑ Li X, He S, Zhou X, Ye Y, Tan S, Zhang S, Li R, Yu M, Jundt MC, Hidebrand A, Wang Y, Li G, Huang C, Wu M (Jan 2016). "Lyn delivers bacteria to lysosomes for eradication through TLR2-initiated autophagy related phagocytosis". PLOS Pathogens. 12 (1): e1005363. doi: 10.1371/journal.ppat.1005363 . PMC   4703367 . PMID   26735693.
  39. ↑ Li X, Zhou X, Ye Y, Li Y, Li J, Privratsky B, Wu E, Gao H, Huang C, Wu M (2012). "Lyn regulates inflammatory responses in Klebsiella pneumonia infection via the p38/NF-kB pathway". Eur. J. Immunol. 44 (3): 763–773. doi:10.1002/eji.201343972. PMC   4103995 . PMID   24338528.
  40. ↑ Wang X, Li Y, Wang X, Zhang Y, Liu Z, Zhong N, Wu M, Li G (Feb 2016). "Lyn regulates mucus secretion and MUC5AC via the STAT6 signaling pathway during allergic airway inflammation". Sci Rep. 7: 42675. doi: 10.1038/srep42675 . PMC   5312001 . PMID   28205598.
  41. ↑ Hibbs ML, Harder KW, Armes J, Kountouri N, Quilici C, Casagranda F, Dunn AR, Tarlinton DM (Dec 2002). "Sustained activation of Lyn tyrosine kinase in vivo leads to autoimmunity". The Journal of Experimental Medicine. 196 (12): 1593–604. doi:10.1084/jem.20020515. PMC   2196073 . PMID   12486102.
  42. 1 2 Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H, Druker BJ, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin JD, Golemis EA, Freedman AS (Feb 1997). "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". The Journal of Biological Chemistry. 272 (7): 4230–6. doi: 10.1074/jbc.272.7.4230 . hdl: 20.500.12613/9177 . PMID   9020138.
  43. ↑ Qiu W, Cobb RR, Scholz W (May 1998). "Inhibition of p130cas tyrosine phosphorylation by calyculin A". Journal of Leukocyte Biology. 63 (5): 631–5. doi: 10.1002/jlb.63.5.631 . PMID   9581808. S2CID   11177730.
  44. 1 2 Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (Apr 2002). "Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling". The Journal of Biological Chemistry. 277 (16): 13732–8. doi: 10.1074/jbc.M200277200 . PMID   11825908.
  45. ↑ Linnekin D, DeBerry CS, Mou S (Oct 1997). "Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells". The Journal of Biological Chemistry. 272 (43): 27450–5. doi: 10.1074/jbc.272.43.27450 . PMID   9341198.
  46. ↑ Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (Jun 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry. 275 (23): 17420–7. doi: 10.1074/jbc.M001892200 . PMID   10748054.
  47. ↑ Greer SF, Justement LB (May 1999). "CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1". Journal of Immunology. 162 (9): 5278–86. doi: 10.4049/jimmunol.162.9.5278 . PMID   10228003.
  48. ↑ Kharbanda S, Yuan ZM, Rubin E, Weichselbaum R, Kufe D (Aug 1994). "Activation of Src-like p56/p53lyn tyrosine kinase by ionizing radiation". The Journal of Biological Chemistry. 269 (32): 20739–43. doi: 10.1016/S0021-9258(17)32054-9 . PMID   8051175.
  49. ↑ Pathan NI, Geahlen RL, Harrison ML (Nov 1996). "The protein-tyrosine kinase Lck associates with and is phosphorylated by Cdc2". The Journal of Biological Chemistry. 271 (44): 27517–23. doi: 10.1074/jbc.271.44.27517 . PMID   8910336.
  50. ↑ van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (Nov 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood. 96 (10): 3406–13. doi:10.1182/blood.V96.10.3406. hdl: 1765/9530 . PMID   11071635.
  51. ↑ Chin H, Arai A, Wakao H, Kamiyama R, Miyasaka N, Miura O (May 1998). "Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway". Blood. 91 (10): 3734–45. doi: 10.1182/blood.V91.10.3734 . PMID   9573010.
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